Women rule.

Female animals tolerate trauma and hemorrhage better than male animals AND Estrogen has rapid nongenomic effects that protect organs from damage and attenuate insult-induced inflammation MOREOVER The survival deficit from trauma and hemorrhage produced in ovariectomized female animals is repaired with administration of exogenous estrogen AND Women survive injury, sepsis, and trauma-hemorrhage-induced hypoxemia/reperfusion better than men THEREFORE Women rule ... in survival after trauma, thus, men would benefit from being more like women.

Protein C depletion early after trauma increases the risk of ventilator-associated pneumonia.

INTRODUCTION: Mechanically ventilated trauma patients have a high risk for the development of ventilator-associated pneumonia (VAP). We have recently reported that reduced plasma protein C (PC) levels early after trauma/shock are associated with coagulopathy and mortality. Furthermore, trauma patients with tissue injury and shock are at higher risk for the development of VAP. OBJECTIVE: We hypothesized that low PC levels early after trauma are associated with an increased susceptibility to VAP in trauma patients. METHODS: Fifty-nine acutely injured, intubated trauma patients were admitted to the critical care unit. Serial blood samples were drawn and coagulation factors were measured. VAP was diagnosed by presence of bacteria on bronchial alveolar lavage specimen, bilateral infiltrates on chest roentgenogram, and fever or elevated white blood cell count. RESULTS: There were no differences in demographic or injury characteristics between patients who developed VAP and those who did not. As expected, patients who developed VAP had more ventilator days, hospital days, intensive care unit days, and greater mortality (all p < 0.05). Patients in both groups had lower mean PC levels at 6 hours compared with baseline. Noninfected patients' PC subsequently returned to near baseline levels, whereas those patients who eventually acquired VAP had significantly lower PC levels at both 12 and 24 hours (12 hours: 79 vs. 96%, p = 0.05; 24 hours: 75 vs. 97% p = 0.02). Soluble endothelial PC receptor (sEPCR) levels were also lower at 24 hours (82 vs. 99% in the noninfected group, p = 0.04). DISCUSSION: The activation of PC pathway early after trauma may protect the vascular endothelium by both its anticoagulant and cytoprotective effects. However, trauma patients who later developed VAP have significantly lower plasma levels of PC within 24 hours after injury, suggesting a possible consumption of this vitamin K-dependent protein and an inhibition of its activation by inflammatory mediators. EPCR is involved in the activation of PC and is also a mediator of its cytoprotective effects. CONCLUSION: Critically ill trauma patients have an early activation of the PC pathway, associated with a rapid decrease in the plasma levels of this protein and increase in EPCR. Plasma levels of PC return to normal levels within 24 hours in most patients. However, patients who go on to acquire VAP have persistently low plasma levels of PC in the immediate period after trauma. Whether PC could play a mechanistic role in the host response against nosocomial lung infection warrants further study.

Fondaparinux for prevention of venous thromboembolism in high-risk trauma patients: a pilot study.

BACKGROUND: Venous thromboembolic events (VTE) remain a major cause of morbidity and mortality after trauma. Fondaparinux, a synthetic, nonheparin drug, has shown promise in reducing VTE in orthopaedic patients, but has not previously been studied in trauma patients. The goal of this study was to determine the safety and efficacy of fondaparinux when incorporated into our VTE prevention protocol. We hypothesized that the occult deep vein thrombosis (DVT) rate in high-risk patients receiving fondaparinux would be <5%. STUDY DESIGN: Consented patients were assigned to a treatment group stratified by their VTE risk factors: high-risk, fondaparinux 2.5 mg subcutaneously once daily; very high-risk, both fondaparinux and pneumatic compression. Patients who were not candidates for anticoagulation received pneumatic compression only. All patients underwent surveillance venous ultrasonography imaging of upper and lower extremities on enrollment and weekly thereafter. Serum samples were analyzed for peak and trough drug concentration levels. RESULTS: Overall incidence of DVT among the 87 enrolled patients was 4.6%. DVT developed in only 1 of 80 patients who received fondaparinux (1.2%). One patient assigned to fondaparinux had a DVT on initial scan before receiving prophylaxis. DVT developed in two of six patients in pneumatic compression only (33%). There were no episodes of pulmonary embolism, thrombocytopenia, or bleeding attributable to fondaparinux. Serum levels indicated adequate absorption of the drug and an effective dosing regimen. CONCLUSIONS: Fondaparinux appears to offer protection against VTE in high-risk trauma patients. Its once-daily dosing regimen can improve compliance and reduce cost and eliminate risk of heparin-induced thrombocytopenia.

Angiopoietin-2, marker and mediator of endothelial activation with prognostic significance early after trauma?

OBJECTIVE: To measure plasma levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) early after trauma and to determine their clinical significance. BACKGROUND: Angiopoietins and VEGF play a central role in the physiology and pathophysiology of endothelial cells. Ang-2 has recently been shown to have pathogenetic significance in sepsis and acute lung injury. Little is known about the role of angiopoietins and VEGF early after trauma. METHODS: Blood specimens from consecutive major trauma patients were obtained immediately upon arrival in the emergency department and plasma samples assayed for Ang-1, Ang-2, VEGF, markers of endothelial activation, protein C pathway, fibrinolytic system, and complement. Base deficit was used as a measure of tissue hypoperfusion. Data were collected prospectively. RESULTS: Blood samples were obtained from 208 adult trauma patients within 30 minutes after injury before any significant fluid resuscitation. Plasma levels of Ang-2, but not Ang-1 and VEGF were increased and correlated independently with severity of injury and tissue hypoperfusion. Furthermore, plasma levels of Ang-2 correlated with markers of endothelial activation, coagulation abnormalities, and activation of the complement cascade and were associated with worse clinical outcome. CONCLUSIONS: Ang-2 is released early after trauma with the degree proportional to both injury severity and systemic hypoperfusion. High levels of Ang-2 were associated with an activated endothelium, coagulation abnormalities, complement activation, and worse clinical outcome. These data indicate that Ang-2 is a marker and possibly a direct mediator of endothelial activation and dysfunction after severe trauma.